Trial Outcomes & Findings for A 52-Week Parallel Group Safety Study of TD-4208 in Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02518139)

Last Updated: 2022-02-24

Results Overview

To assess the safety and tolerability of TD-4208 by assessing the frequency and severity of Treatment Emergent Adverse Events (TEAE)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1060 participants

Primary outcome timeframe

Baseline to Day 365

Results posted on

2022-02-24

Participant Flow

Participant milestones

Participant milestones
Measure	TD-4208-1 88 mcg TD-4208: There is not a placebo, there is a comparator (Tiotropium) arm, and the subjects are blinded to one of two doses of 4208 or un-blinded to Tiotropium.	TD-4208-2 175 mcg TD-4208: There is not a placebo, there is a comparator (Tiotropium) arm, and the subjects are blinded to one of two doses of 4208 or un-blinded to Tiotropium.	Tiotropium 18 mcg Tiotropium: Active comparator
Overall Study STARTED	364	335	356
Overall Study COMPLETED	219	191	262
Overall Study NOT COMPLETED	145	144	94

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A 52-Week Parallel Group Safety Study of TD-4208 in Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TD-4208-1 n=364 Participants 88 mcg TD-4208: There is not a placebo, there is a comparator (Tiotropium) arm, and the subjects are blinded to one of two doses of 4208 or un-blinded to Tiotropium.	TD-4208-2 n=335 Participants 175 mcg TD-4208: There is not a placebo, there is a comparator (Tiotropium) arm, and the subjects are blinded to one of two doses of 4208 or un-blinded to Tiotropium.	Tiotropium n=356 Participants 18 mcg Tiotropium: Active comparator	Total n=1055 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	183 Participants n=5 Participants	167 Participants n=7 Participants	163 Participants n=5 Participants	513 Participants n=4 Participants
Age, Categorical >=65 years	181 Participants n=5 Participants	168 Participants n=7 Participants	193 Participants n=5 Participants	542 Participants n=4 Participants
Age, Continuous	64.1 years STANDARD_DEVIATION 9.36 • n=5 Participants	64.4 years STANDARD_DEVIATION 8.61 • n=7 Participants	64.9 years STANDARD_DEVIATION 8.91 • n=5 Participants	64.4 years STANDARD_DEVIATION 8.97 • n=4 Participants
Sex: Female, Male Female	158 Participants n=5 Participants	139 Participants n=7 Participants	142 Participants n=5 Participants	439 Participants n=4 Participants
Sex: Female, Male Male	206 Participants n=5 Participants	196 Participants n=7 Participants	214 Participants n=5 Participants	616 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	357 Participants n=5 Participants	326 Participants n=7 Participants	352 Participants n=5 Participants	1035 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	24 Participants n=5 Participants	21 Participants n=7 Participants	24 Participants n=5 Participants	69 Participants n=4 Participants
Race (NIH/OMB) White	337 Participants n=5 Participants	309 Participants n=7 Participants	331 Participants n=5 Participants	977 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United States	364 participants n=5 Participants	335 participants n=7 Participants	356 participants n=5 Participants	1055 participants n=4 Participants
Smoking Status Current Smoker	171 Participants n=5 Participants	151 Participants n=7 Participants	167 Participants n=5 Participants	489 Participants n=4 Participants
Smoking Status Former Smoker	193 Participants n=5 Participants	184 Participants n=7 Participants	189 Participants n=5 Participants	566 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Day 365

To assess the safety and tolerability of TD-4208 by assessing the frequency and severity of Treatment Emergent Adverse Events (TEAE)

Outcome measures

Outcome measures
Measure	TD-4208-1 n=364 Participants 88 mcg TD-4208	TD-4208-2 n=335 Participants 175 mcg TD-4208	Tiotropium n=356 Participants 18 mcg Tiotropium: Active comparator
Adverse Events: Frequency and Severity Adverse Event (AE)	272 Participants	242 Participants	275 Participants
Adverse Events: Frequency and Severity Moderate or Severe AE	226 Participants	174 Participants	210 Participants
Adverse Events: Frequency and Severity Serious AE	58 Participants	43 Participants	58 Participants

Adverse Events

TD-4208-1

Serious events: 58 serious events

Other events: 202 other events

Deaths: 1 deaths

TD-4208-2

Serious events: 43 serious events

Other events: 166 other events

Deaths: 1 deaths

Tiotropium

Serious events: 58 serious events

Other events: 188 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Clinical Development & Medical Affairs

Theravance Biopharma

Phone: 1-855-633-8479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI may communicate the trial results generated by the PI, but only after the first publication or presentation of the combined study results generated by all participating sites. The Sponsor can then review trial results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The Sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	TD-4208-1 n=364 participants at risk 88 mcg TD-4208: There is not a placebo, there is a comparator (Tiotropium) arm, and the subjects are blinded to one of two doses of 4208 or un-blinded to Tiotropium.	TD-4208-2 n=335 participants at risk 175 mcg TD-4208: There is not a placebo, there is a comparator (Tiotropium) arm, and the subjects are blinded to one of two doses of 4208 or un-blinded to Tiotropium.	Tiotropium n=356 participants at risk 18 mcg Tiotropium: Active comparator
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	29.4% 107/364 • Number of events 107 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	21.8% 73/335 • Number of events 73 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	28.1% 100/356 • Number of events 100 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Infections and infestations Nasopharyngitis	7.7% 28/364 • Number of events 28 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	7.8% 26/335 • Number of events 26 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	4.8% 17/356 • Number of events 17 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Infections and infestations Upper Respiratory Tract Infection	6.6% 24/364 • Number of events 24 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	6.0% 20/335 • Number of events 20 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	6.7% 24/356 • Number of events 24 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Cough	4.9% 18/364 • Number of events 18 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	7.5% 25/335 • Number of events 25 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	5.6% 20/356 • Number of events 20 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.5% 31/364 • Number of events 31 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	3.9% 13/335 • Number of events 13 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	3.7% 13/356 • Number of events 13 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Nervous system disorders Headache	4.1% 15/364 • Number of events 15 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	3.9% 13/335 • Number of events 13 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	5.6% 20/356 • Number of events 20 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Infections and infestations Urinary tract infection	5.5% 20/364 • Number of events 20 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	3.3% 11/335 • Number of events 11 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	4.2% 15/356 • Number of events 15 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Infections and infestations Bronchitis	4.7% 17/364 • Number of events 17 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	5.1% 17/335 • Number of events 17 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	2.5% 9/356 • Number of events 9 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Vascular disorders Hypertension	4.9% 18/364 • Number of events 18 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	2.4% 8/335 • Number of events 8 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	4.5% 16/356 • Number of events 16 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Gastrointestinal disorders Diarrhoea	3.8% 14/364 • Number of events 14 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	3.9% 13/335 • Number of events 13 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	2.5% 9/356 • Number of events 9 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Respiratory, thoracic and mediastinal disorders Pneumonia	4.4% 16/364 • Number of events 16 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	1.5% 5/335 • Number of events 5 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	3.9% 14/356 • Number of events 14 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Infections and infestations Sinusitis	4.1% 15/364 • Number of events 15 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	2.4% 8/335 • Number of events 8 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	2.5% 9/356 • Number of events 9 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Musculoskeletal and connective tissue disorders Back Pain	2.7% 10/364 • Number of events 10 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	2.1% 7/335 • Number of events 7 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	2.8% 10/356 • Number of events 10 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Musculoskeletal and connective tissue disorders Anthralgia	2.5% 9/364 • Number of events 9 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	1.8% 6/335 • Number of events 6 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	3.1% 11/356 • Number of events 11 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Gastrointestinal disorders Nausea	1.9% 7/364 • Number of events 7 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	1.8% 6/335 • Number of events 6 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	3.4% 12/356 • Number of events 12 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)
Gastrointestinal disorders Gastrooesophageal reflux disease	2.2% 8/364 • Number of events 8 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	2.4% 8/335 • Number of events 8 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)	2.2% 8/356 • Number of events 8 • Adverse events were recorded from signing of the ICF through the final follow-up assessment (approximately 1 year)